The overall goal of this proposal is to provide the resources and experiences that will allow the applicant to develop into a methodologically sophisticated, independent clinical investigator pursuing a research agenda directed at the effects of alcohol use and other comorbidity on the progression of HIV disease. This long term goal will be attained through the mentored completion of a study designed to improve tailoring of HIV treatment strategies to alcohol using populations. Using a large, ongoing prospective observational cohort (the Veterans Administration Cohort Study) the applicant will analyze the associations of alcohol use with short- and long-term efficacy of Highly-Active Anti-Retroviral Therapy (HAART). These associations will then be used in a computer simulation that will explore questions that clinical trials are not well suited to answer. The particular treatment questions that will be examined in this proposal are (1) how much life expectancy would be increased by treating hazardous or harmful patterns of alcohol consumption (2) what clinical parameters (CD4 and/or viral load) are the most appropriate thresholds for starting HAART, (3) what clinical parameters are the most appropriate thresholds for switching HAART upon regimen failure. The skills necessary to accomplish the above objectives and become an independent researcher will be accomplished through a series of classes, seminars, and mentored, structured reading and tutorials directed at specific areas of research related to the research proposal. The centerpiece of career development activities will be the K30 supported Clinical Research Training Program at the University of Pittsburgh which leads to a Masters Degree in Clinical Research. This program will be augmented through substantial time with internationally renowned experts and courses outside the Masters Degree program with specific applicability to important subject domains in the proposal, such as measurement of alcohol use and its consequences, measurement of adherence patterns and their correlates, survival analysis, regression analysis with time-dependent covariates, and algorithm design. My primary mentor, Mark S. Roberts, MD, MPP, an expert in medical decision sciences, together with my co-mentor, Amy Justice, the Principle Investigator of the Veterans Administration Cohort Study, will provide weekly feedback and supervision to help me accomplish these objectives.